[1]毛新志,童宏方,戴和平,等.内质网应激前列腺癌细胞通过STAT3信号途径促进巨噬细胞M2极化的研究[J].医学信息,2022,35(03):74-80,102.[doi:10.3969/j.issn.1006-1959.2022.03.018]
　MAO Xin-zhi,TONG Hong-fang,DAI He-ping,et al.Endoplasmic Reticulum Stressed Prostate Cancer Cells Promotes Macrophage M2Polarization Through STAT3 Signaling Pathway[J].Medical Information,2022,35(03):74-80,102.[doi:10.3969/j.issn.1006-1959.2022.03.018]
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内质网应激前列腺癌细胞通过STAT3信号途径促进巨噬细胞M2极化的研究()
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医学信息[ISSN:1006-1959/CN:61-1278/R]

卷:
35卷
期数:
2022年03期
页码:
74-80,102
栏目:
论著
出版日期:
2022-02-01

文章信息/Info

Title:
Endoplasmic Reticulum Stressed Prostate Cancer Cells Promotes Macrophage M2Polarization Through STAT3 Signaling Pathway
文章编号:
1006-1959（2022）03-0074-08
作者:
毛新志; 童宏方; 戴和平; 淡彬志; 朱 梅
安徽医科大学附属巢湖医院检验科，安徽 巢湖 238000
Author(s):
MAO Xin-zhi; TONG Hong-fang; DAI He-ping; DAN Bin-zhi; ZHU Mei
Department of Laboratory,Chaohu Hospital Affiliated to Anhui Medical University,Chaohu 238000,Anhui,China
关键词:
内质网应激; 前列腺癌; 外泌体; STAT3; 巨噬细胞极化
Keywords:
Endoplasmic reticulum stress; Prostate cancer; Exosomes; STAT3; Macrophage polarization
分类号:
R737.25
DOI:
10.3969/j.issn.1006-1959.2022.03.018
文献标志码:
A
摘要:
目的 探讨前列腺癌细胞内质网应激相关外泌体能否通过STAT3调控巨噬细胞M2极化。方法 以有无毒胡萝卜素（TG）刺激，将前列腺癌细胞（PC3）细胞分为TG组和Con组。TG组分别以不同浓度TG同样时间和同样浓度TG不同时间刺激PC3细胞，通过观察ERS标志蛋白GRP78的表达，确定最佳刺激浓度与时间；Western blot检测Con组和TG组外泌体标志蛋白CD63和TSG101表达，透射电子显微镜鉴定外泌体；激光共聚焦显微镜观察巨噬细胞摄取外泌体；以Con组和TG组外泌体刺激巨噬细胞分为M-Con组和M-TG组，化学发光法检测M-TG组和M-Con组巨噬细胞炎症因子IL-1β、IL-6、IL-10与TNF-α表达情况；Western blot检测M-TG组和M-Con组巨噬细胞PD-L1表达及STAT3通路蛋白表达。结果 以TG刺激PC3细胞，结果显示当以3 μmol/L的TG刺激PC3细胞24 h，可明显升高GRP78蛋白的表达，可以构建较好的前列腺癌细胞ERS模型。Western blot及透视电镜结果证实成功分离PC3外泌体，且TG组外泌体表达CD63与TSG101多于Con组（P＜0.05）；激光共聚焦显微镜显示，外泌体能够被巨噬细胞所吞噬；化学发光结果显示，M-TG组分泌的炎症因子较M-Con组多（P＜0.05），能够完成巨噬细胞的M2极化；与 M-Con组比较，M-TG组能增加巨噬细胞PD-L1蛋白表达，并且激活巨噬细胞STAT3通路（P＜0.05）。结论 内质网应激的前列腺癌细胞可能通过释放外泌体，激活巨噬细胞STAT3通路，上调巨噬细胞PD-L1蛋白表达，促进巨噬细胞M2极化。
Abstract:
Objective To investigate whether endoplasmic reticulum stress-associated exosomes in prostate cancer cells can regulate macrophage M2 polarization via STAT3.Methods Prostate cancer cells (PC3) were stimulated with non-toxic carotene (TG) and divided into TG group and Con group. In the TG group, PC3 cells were stimulated at the same time with different concentrations of TG and at different times with the same concentration of TG, and the optimal stimulation concentration and time were determined by observing the expression of ERS marker protein GRP78 ; the expression of exosome marker proteins CD63 and TSG101 in Con group and TG group was detected by Western blot, and exosomes were identified by transmission electron microscope. Laser confocal microscope was used to observe the uptake of exosomes by macrophages ; macrophages stimulated by exosomes in Con group and TG group were divided into M-Con group and M-TG group. The expressions of inflammatory factors IL-1β, IL-6, IL-10 and TNF-α in M-TG group and M-Con group were detected by chemiluminescence method. Western blot was used to detect PD-L1 expression and STAT3 pathway protein expression in macrophages of M-TG and M-Con groups.Results PC3 cells were stimulated by TG, the results showed that the expression of GRP78 protein was significantly increased when PC3 cells were stimulated by 3 μmol/L TG for 24 h, and a better ERS model of prostate cancer cells could be constructed. Western blot and transmission electron microscopy confirmed the successful isolation of PC3 exosomes, and the expression of CD63 and TSG101 in the exosomes of the TG group was higher than that of the Con group (P<0.05). Laser confocal microscopy showed that exosomes could be swallowed by macrophages ; the chemiluminescence results showed that the M-TG group secreted more inflammatory factors than the M-Con group (P<0.05), which could complete the M2 polarization of macrophages. Compared with the M-Con group, the M-TG group could increase the expression of PD-L1 protein in macrophages and activate the STAT3 pathway in macrophages (P<0.05).Conclusion Endoplasmic reticulum stress prostate cancer cells may activate STAT3 pathway of macrophages by releasing exosomes, up-regulate PD-L1 protein expression of macrophages, and promote M2 polarization of macrophages.

参考文献/References:

[1]Henley SJ,Ward EM,Scott S,et al.Annual report to the nation on the status of cancer， part I: National cancer statistics[J].Cancer,2020,126(10):2225-2249.[2]Zhan F,Shen J,Wang R,et al.Role of exosomal small RNA in prostate cancer metastasis[J].Cancer Manag Res,2018(10):4029-4038. [3]Wang G,Zhao D,Spring DJ,et al.Genetics and biology of prostate cancer[J].Genes Dev,2018,32(17-18):1105-1140. [4]Ramirez MU,Hernandez SR,Soto-Pantoja DR,et al.Endoplasmic Reticulum Stress Pathway, the Unfolded Protein Response, Modulates Immune Function in the Tumor Microenvironment to Impact Tumor Progression and Therapeutic Response[J].Int J Mol Sci,2019,21(1):169.[5]Cubillos-Ruiz JR,Bettigole SE,Glimcher LH.Tumorigenic and Immunosuppressive Effects of Endoplasmic Reticulum Stress in Cancer[J].Cell,2017,168(4):692-706.[6]Wu K,Lin K,Li X,et al.Redefining Tumor-Associated Macrophage Subpopulations and Functions in the Tumor Microenvironment[J].Front Immunol,2020(11):1731.[7]Díaz-Bulnes P,Saiz ML,López-Larrea C,et al.Crosstalk Between Hypoxia and ER Stress Response: A Key Regulator of Macrophage Polarization[J].Front Immunol,2020(10):2951.[8]Liu J,Fan L,Yu H,et al.Endoplasmic Reticulum Stress Causes Liver Cancer Cells to Release Exosomal miR-23a-3p and Up-regulate Programmed Death Ligand 1 Expression in Macrophages[J].Hepatology,2019,70(1):241-258.[9]Zou S,Tong Q,Liu B,et al.Targeting STAT3 in Cancer Immunotherapy[J].Mol Cancer,2020,19(1):145.[10]He W,Zhu Y,Mu R,et al.A Jak2-selective inhibitor potently reverses the immune suppression by modulating the tumor microenvironment for cancer immunotherapy[J].Biochem Pharmacol,2017(145):132-146.[11]Oakes SA.Endoplasmic Reticulum Stress Signaling in Cancer Cells[J].Am J Pathol,2020,190(5):934-946.[12]Xue X,Zhao Y,Wang X,et al.Development and validation of serum exosomal microRNAs as diagnostic and prognostic biomarkers for hepatocellular carcinoma[J].J Cell Biochem, 2019,120(1):135-142.[13]Roman-Canal B,Moiola CP,Gatius S,et al.EV-Associated miRNAs from Peritoneal Lavage are a Source of Biomarkers in Endometrial Cancer[J].Cancers (Basel),2019,11(6):839.[14]Piao YJ,Kim HS,Hwang EH,et al.Breast cancer cell-derived exosomes and macrophage polarization are associated with lymph node metastasis[J].Oncotarget,2017,9(7):7398-7410. [15]Ibrahim IM,Abdelmalek DH,Elfiky AA.GRP78: A cell’s response to stress[J].Life Sci,2019(226):156-163.[16]Wang LX,Zhang SX,Wu HJ,et al.M2b macrophage polarization and its roles in diseases[J].J Leukoc Biol,2019,106(2):345-358.[17]Bardi GT,Smith MA,Hood JL.Melanoma exosomes promote mixed M1 and M2 macrophage polarization[J].Cytokine,2018(105):63-72.[18]张文涛,杨伟江,罗杰夫,等.ALA-PDT通过NF-kB通路调节巨噬细胞极化状态[J].激光杂志,2021,42(3):197-201.[19]Li M,Li M,Yang Y,et al.Remodeling tumor immune microenvironment via targeted blockade of PI3K-γ and CSF-1/CSF-1R pathways in tumor associated macrophages for pancreatic cancer therapy[J].J Control Release,2020(321):23-35.[20]Kataoka K.Regulatory mechanisms of PD-L1 expression and its role in immune evasion[J].Gan To Kagaku Ryoho,2017(44):967-971.[21]Mu X,Shi W,Xu Y,et al.Tumor-derived lactate induces M2 macrophage polarization via the activation of the ERK/STAT3 signaling pathway in breast cancer[J].Cell Cycle,2018,17(4):428-438.[22]Tkach M,Théry C.Communication by Extracellular Vesicles: Where We Are and Where We Need to Go[J].Cell,2016,164(6):1226-1232.[23]Solís-Martínez R,Cancino-Marentes M,Hernández-Flores G,et al.Regulation of immunophenotype modulation of monocytes-macrophages from M1 into M2 by prostate cancer cell-culture supernatant via transcription factor STAT3[J].ImmunolLett,2018(196):140-148.[24]Cui L,Yang G,Ye J,et al.Dioscin elicits anti-tumour immunity by inhibiting macrophage M2 polarization via JNK and STAT3 pathways in lung cancer[J].J Cell Mol Med,2020,24(16):9217-9230.[25]Rong J,Xu L,Hu Y,et al.Inhibition of let-7b-5p contributes to an anti-tumorigenic macrophage phenotype through the SOCS1/STAT pathway in prostate cancer[J].Cancer Cell Int,2020(20):470.

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更新日期/Last Update: 1900-01-01